Baicalin attenuates non-alcoholic steatohepatitis by suppressing key regulators of lipid metabolism, inflammation and fibrosis in mice
Baicalin attenuates non-alcoholic steatohepatitis by suppressing key regulators of lipid metabolism, inflammation and fibrosis in mice
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黄芩苷通过抑制小鼠脂质代谢、炎症和纤维化的关键调节因子来减轻非酒精性脂肪性肝炎
DOI：
10.1016/j.lfs.2017.11.027
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发表时间：
2018
期刊：
影响因子：
6.1
通讯作者：
Xu Keshu
中科院分区：
文献类型：
--
作者：
Zhang Junli;Zhang Haiming;Deng Xiaoling;Zhang Ning;Liu Beibei;Xin Shengliang;Li Guixin;Xu Keshu
黄芩苷（Baicalin，BA）是一种来源于黄芩的黄酮类化合物，具有抗炎和抗氧化作用。然而，BA在调节非酒精性脂肪性肝炎（NASH）中的潜在作用仍然难以捉摸。在这项研究中，我们新探索了BA在MCD饮食诱导的NASH中的保肝作用，通过改善肝脏脂肪变性、炎症、纤维化和凋亡。同时用或不用BA处理小鼠4周。分别采用生化法和ELISA法检测血清肝功能指标和炎症指标。用H&E、油红O和Masson三色染色法对肝脏进行组织学检查。结果表明：BA处理可显著减轻MCD饲料诱导的肝脏脂质沉积，其机制可能与调节SREBP-1c、FRES 1、PPARα和CPT 1a的表达有关。BA处理显著抑制MCD饲料诱导的肝脏炎症，这与血清TNF-α、IL-1β和MCP-1产生减少、巨噬细胞内流和核因子-κB活化抑制有关。此外，BA被证明可以防止肝纤维化，这似乎是通过抑制α-SMA，TGF-β1和Col 1A 1介导的。BA还能显著抑制MCD饮食诱导的小鼠肝细胞凋亡和caspase-3蛋白的表达，这些结果为BA治疗NASH提供了可能的机制。
AimsBaicalin (BA), an active flavonoid compound originating from the herb ofScutellaria baicalensis Georgi, has been previously shown to exert anti-inflammation and anti-oxidant effects in liver diseases. However, the potential role of BA in the regulation of non-alcoholic steatohepatitis (NASH) remains elusive. In this study, we newly explored the hepatoprotective effects of BA in MCD diet-induced NASH by ameliorating hepatic steatosis, inflammation, fibrosis and apoptosis.Main methodsNASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4 weeks. The mice were simultaneously treated with or without BA for 4 weeks. Serum liver functional markers and inflammatory indicators were assessed by biochemical and ELISA methods, respectively. The livers were histologically examined using H&E, Oil Red O and Masson's trichrome staining methods. The qRT-PCR, IHC and Western blotting assays were applied to analyze mechanisms underlying BA protection.Key findingsBA treatment significantly attenuated MCD diet-induced hepatic lipid accumulation partly through regulating the expression of SREBP-1c, FASN, PPARα and CPT1a. BA treatment dramatically suppressed MCD diet-induced hepatic inflammation, which was associated with decrease in serum TNF-α, IL-1β and MCP-1 production, macrophage influx and suppression of nuclear factor-κB activation. Additionally, BA was proved to prevent liver fibrosis, which appears to be mediated by inhibition of α-SMA, TGF-β1 and Col1A1. Furthermore, BA markedly inhibited hepatocyte apoptosis and cleaved caspase-3 protein expression in MCD diet-induced mice.SignificanceThese results provide a possible basis of the underlying mechanism for the application of BA in the treatment of NASH.